A time-of-flight mass spectrometer (hereinafter abbreviated as TOFMS) is a type of device used for measuring the time of flight required for each ion to travel a specific distance and converting the time of flight to the mass-to-charge ratio to create a mass spectrum. This is based on the principle that ions accelerated by a certain amount of energy will fly at different speeds corresponding to their mass-to-charge ratio. Accordingly, elongating the flight distance of the ions is effective for enhancing the mass resolving power. However, elongating the flight distance along a straight line requires enlarging the device. To solve this problem, multi-turn time-of-flight mass spectrometers (hereinafter abbreviated as MT-TOFMS) have been developed, in which ions are made to repeatedly fly along a closed orbit having a substantially circular shape, substantially elliptical shape, substantially figure-“8” shape or other shape in order to simultaneously achieve both the elongation of the flight distance and the downsizing of the apparatus.
Another type of device developed for the same purpose is the multi-reflection time-of-flight mass spectrometer, in which the aforementioned loop orbit is replaced by a reciprocating path in which a reflecting electric field is created to make ions fly back and forth multiple times and thereby elongate their flight distance. Although the multi-turn time-of-flight type and the multi-reflection time-of-flight type use different ion optical systems, they are essentially based on the same principle for improving the mass resolving power and are intended for addressing the same problem. Accordingly, in the present description, the “multi-turn time-of-flight type” should be interpreted as inclusive of the “multi-reflection time-of-flight type.”
As previously described, MT-TOFMSs can achieve a high level of mass-resolving power by elongating the flight distance. However, they have a drawback due to the fact that the flight path of the ions is a closed orbit. That is, as the number of turns of the ions increases, an ion having a smaller mass-to-charge ratio and flying at a higher speed overtakes another ion having a larger mass-to-charge ratio and flying at a lower speed. If such an overtaking of ions having different mass-to-charge ratios occurs, the obtained time-of-flight spectrum will have a mixture of peaks originating from the ions that have undergone different numbers of turns. That is to say, it is possible that the flight distance of the ion corresponding to one peak differs from that of the ion corresponding to another peak. This means it is no longer ensured that the mass-to-charge ratio and the flight distance uniquely correspond to each other, so that the time-of-flight spectrum cannot be directly converted to a mass spectrum.
To address the aforementioned drawback, in many conventional MT-TOFMSs, the ions originating from a sample generated in an ion source are subjected to an ion-filtering process beforehand (i.e. before being introduced into the loop orbit) to select only a group of ions belonging to a mass-to-charge ratio range where the aforementioned overtaking will not occur. The selected ions are made to fly along the loop orbit to undergo a predetermined number of turns and then be detected. Although a mass spectrum with a high mass resolving power can be obtained with such a method, the mass-to-charge ratio range of the obtained mass spectrum is significantly limited. This is contrary to the advantage of TOFMSs that a mass spectrum with a relatively wide mass-to-charge ratio range can be obtained by one cycle of measurement.
To address such problems, various methods have been proposed for creating a mass spectrum from a time-of-flight spectrum obtained by a measurement even if the overtaking of ions occurs during their flight in the loop orbit.
For example, Patent Document 1 discloses a method in which a plurality of time-of-flight spectra for different periods of time for ejection of the ions from the orbit are obtained for a target sample and then a time-of-flight spectrum of a single turn is reconstructed using a multi-correlation function of the plural different time-of-flight spectra. The “period of time for ejection of an ion” is generally the amount of time from the point in time when the ion is ejected from an ion source until the point in time when the ion is made to deviate from the loop orbit after passing through this orbit. Hereinafter, this will be simply referred to as the “ion ejection time.” With this method, obtaining a mass spectrum substantially in real time while performing the measurement is almost impossible because of the large amount of computation of the multi-correlation function, which requires considerable computing time. Furthermore, if a significantly large number of peaks appear on the time-of-flight spectra, the amount of computation becomes enormous. In such a case, it is difficult to obtain the result of computation in a practically acceptable length of time if a general-purpose personal computer is used.
Another type of method for obtaining a mass spectrum is described in Patent Document 3, as well as Non-Patent Documents 1 and 2. In this method, a time-of-flight spectrum for a target sample is obtained in a linear mode in which ions injected into the apparatus are ejected without flying through a closed loop orbit. (A time-of-flight spectrum obtained in this mode is hereinafter called the “zero-turn time-of-flight spectrum.”) Then, the number of turns and the time of flight in a multi-turn mode, in which an ion may overtake another ion, are predicted from the time of flight of the peaks on the zero-turn time-of-flight spectrum. Based on this prediction, time-of-flight segments, whose widths are determined by considering the time spread of the peaks, are set on the time-of-flight spectrum in the multi-turn mode. Since the peaks included in one segment originate from ions with the same number of turns, the number of turns and the mass-to-charge ratio of all the peaks can be uniquely determined if no adjacent segments overlap each other. Hence, the existence of the overlapping of the segments which are set on the time-of-flight spectrum in the multi-turn mode is judged to search for a condition under which the overlapping does not occur and to fix the segment setting. Since this determines the optimal ejection time when ions should be ejected from the loop orbit, a measurement in the multi-turn mode is performed by controlling the timing for switching the gate electrode for ejecting ions based on this optimal ejection time. Then, a mass spectrum is created from the time-of-flight spectrum obtained as a result of this measurement.
The data processing used in this method is relatively simple and can be performed in almost real time even by a general-purpose personal computer. However, this method is disadvantageous in that the mass spectrum cannot be created if the number of peaks to be observed is so large that no condition to avoid the overlapping of the segments can be found. When the sample to be analyzed is a protein, sugar chain or similar substance, it is anticipated that the segments often overlap. Accordingly, the cases in which this method can be used are significantly limited. Limiting the range of mass-to-charge ratio of the ions introduced into the loop orbit may be another approach to prevent the segments from overlapping. However, this deteriorates the measurement throughput.
Patent Document 2 discloses a method for deducing the mass-to-charge ratio of a target ion by a process including the steps of: obtaining a plurality of time-of-flight spectra of a target sample with different ion ejection times; calculating possible candidates for the mass-to-charge ratio of the target ion by assuming the number of turns for each peak on each of the time-of-flight spectra; and locating a candidate of the mass-to-charge ratio that has been commonly selected on all the time-of-flight spectra.
The data processing used in this method is also relatively simple and can be performed in almost real time with a general-purpose personal computer. Finding the correspondence relationship of the peaks between the different time-of-flight spectra is easy for a small number of peaks. However, this relating process becomes complicated when the number of components contained in the sample is large and the number of peaks appearing on the time-of-flight spectra is accordingly large. Having a large number of peaks also means a high probability of erroneous deduction of the mass-to-charge ratio; that is to say, a mass-to-charge ratio that is actually unrelated to the target ion may accidentally satisfy the conditions of the deduction. Furthermore, the peaks originating from ions having different mass-to-charge ratios become more likely to accidentally overlap each other on a time-of-flight spectrum, which prevents accurate deduction of the mass-to-charge ratio.